Use In Routine Clinical Practice Research Articles

Enhancing Patient-Reported Outcome Measures for Drug Hypersensitivity: A Validated 6-Item Quality-of-Life Questionnaire for Patients With Drug Hypersensitivity

BACKGROUNDDrug hypersensitivity reactions (DHR) can significantly impair patients’ health-related quality of life (HRQoL). However, tools for HRQoL assessment for patients with DHR are time-consuming and remain underutilized. OBJECTIVETo develop and validate an optimized version of the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) designed for everyday clinical use. METHODSItem response theory (IRT), a statistical framework for psychometric measurement, was used to evaluate the 15 questions from the original DrHy-Q for their respective item difficulty, discrimination, and information using prospective data from 243 patients with histories of suspected/confirmed DHR before allergy workup. Accordingly, the best-performing items were identified to develop a 6-item optimized version (DrHy-Q6), which was subsequently validated with another prospective cohort of 156 patients. RESULTSAll 15 items of the original DrHy-Q demonstrated satisfactory parameters in IRT analysis, including very high discrimination (>1.7), appropriate difficulty (in between -1.5 and 1.5) and good information (a high and broad peak in the information curve). Six items with top-ranked IRT parameters were identified to construct an optimized version, which we named the DrHy-Q6. The DrHy-Q6 demonstrated a 1-factor structure with an improved fit compared to the original DrHy-Q (comparative fit index = 0.985, Tucker–Lewis’s index = 0.974), excellent convergent validity (Unadjusted Pearson correlation with the full version = 0.955; adjusted = 0.894, p<0.001), reliability (Cronbach’s α and McDonald’s ω = 0.93), divergent validity (Pearson correlation with all Short Form 12-item Healthy Survey Version 2 [SF-12v2] subscales < 0.60, p<0.001) and discriminant validity (significantly higher scores with multiple DHR labels [42.45 ± 27.26 vs. 32.93 ± 26.66], p=0.013). CONCLUSIONSFrom an IRT perspective, the DrHy-Q and all its constituent items are psychometrically valid for HRQoL assessment. We propose an optimized 6-item version (DrHy-Q6) as an abbreviated alternative for assessing HRQoL in patients with DHR, especially for routine use in clinical practice. Patients and physicians may benefit from its streamlined length and simpler scoring algorithm.

Role of endoscopic duodenojejunal bypass liner in obesity management and glycemic control.

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariat-ric and metabolic surgery. Various endoscopic bariatric and metabolic therapies recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article compre-hensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising endoscopic bariatric and metabolic therapies, named duodenojejunal bypass liner. The duodenojejunal bypass liner mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern ex-ists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongo-ing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to sup-port its routine use in clinical practice.

Remission Depth in Metastatic Hormone-Sensitive Prostate Cancer Is Associated With Prognosis in Patients With Initial Prostate-Specific Antigen Values Above 100 Ng/ML.

Recently, new drugs have caused a paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). Meanwhile, research has identified several prognostic factors of metastatic HSPC. The present study focused on remission depth in metastatic HSPC and evaluated its association with remission depth. We analyzed 427 patients diagnosed with metastatic HSPC with serum initial prostate-specific antigen (PSA) > 100 ng/ml. The nadir serum PSA value was used as a marker of remission depth for each duration to castration resistanceby using receiver operating characteristic (ROC) curves.Cox proportional hazards regression was used to assess for any correlation of progression-free survival (PFS) and overall survival (OS) with the nadir PSA level. The cut-off value for the nadir PSA level per time to castration resistance (TTCR) at three, five, seven, and nine years was calculated. The nadir PSA value alone was able to predict prognosis because of its high sensitivity, high specificity, and high AUC in ROC analysis. The nadir PSA level can be an independent prognostic marker not only for TTCR but also for OS on multivariate analysis. We identified the cut-off value for nadir PSA per TTCR period in patients with metastatic HSPC. The nadir PSA value alone can predict prognosis; this demonstrates utility in routine clinical practice due to its simplicity and accuracy.

557 - Tralokinumab real-world use in adults with atopic dermatitis: baseline characteristics of the first 100 patients recruited to the TRACE study in the United States

Abstract Introduction/Background Tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD) pathogenesis. Numerous clinical studies have established that tralokinumab is an efficacious treatment for patients with moderate-to-severe AD, along with having a favorable safety profile. However, there is a lack of evidence on tralokinumab use in routine clinical practice, where patient management may differ from that defined by clinical trial protocols. Objectives TRACE is a global, real-world study that aims to better understand the effectiveness, safety, and clinical use of tralokinumab in patients with AD in daily practice. Methods TRACE is a global, observational, prospective, single-cohort study of tralokinumab-treated adults with moderate-to-severe AD. Overall, 11 countries across Europe, North America and the Middle East are participating. The primary objective of TRACE is to assess changes in clinical signs and symptoms of AD in patients treated with tralokinumab according to the nationally approved labels. Secondary objectives include safety, quality of life, patient-reported outcomes and treatment adherence. For this interim analysis, the objective was to report the baseline characteristics of the first 100 US patients. Results Overall, 55% of the first 100 US patients initiated on tralokinumab in the TRACE study were female; the majority (54%) were White, followed by 18% Black or African American and 12% Asian. Mean (standard deviation [SD]) age was 46.4 years (18.2) and body mass index was 28.6 kg/m2 (7.7). Patients had a mean disease duration of 13.9 years (SD 16.5), with 46% being biologic-naïve and 54% biologic-experienced. Most patients (88%) had moderate-to-severe AD, with a mean Investigator’s Global Assessment score of 3.2 (SD 0.8); mean Eczema Area and Severity Index was 15.4 (SD 7.9). A heavy symptomatic burden of disease was evident, with a mean eczema-related sleep numerical rating scale (NRS) of 4.2 (SD 3.3) and mean worst daily pruritus NRS of 6.1 (SD 2.6). Patients also reported a substantial impact of AD on quality of life; mean Dermatology Life Quality Index was 13.2 (SD 8.5). Almost one quarter (24%) of patients reported ≥1 atopic comorbidity, with asthma (12%), cardiovascular disease (8%) and autoimmune disease (6%) being the most frequent; 3% of patients had psychiatric illness. Conclusions Initial findings showed that tralokinumab is being prescribed as a first-line biologic treatment option in the US in accordance with the label. Treated patients had a heavy burden of disease with considerable impact on quality of life.

Efficacy and Safety of Low Dose Naltrexone for Chronic Pain

Naltrexone is a mu-opioid receptor antagonist increasingly used as an analgesic for chronic pain at low doses. This retrospective, observational cohort study was conducted at an academic medical center to evaluate low-dose naltrexone (LDN) efficacy and describe its use in routine clinical practice. Adults receiving LDN, doses <10 mg for ≥1 month, seen at an outpatient pain clinic from January 1, 2014 to April 1, 2022 were included. The primary outcome was change in the Pain, Enjoyment of Life, and General Activity (PEG) score after LDN. Thirty-one patients were included. Median age was 50 years and 71% were female. Median duration of pain at baseline was 5 years. Mean PEG scores were 7.27 ± 1.39 and 6.62 ± 2.04 at baseline and follow-up, respectively. Mean difference was 0.66 (95% CI [0.10–1.21], p = 0.022). Eighty-seven percent (27) of patients discontinued LDN, 52% (16) for lack of benefit, 23% (7) for loss of benefit, 10% (3) for side effects, and 3% (1) for other reasons. Seven (23%) reported side effects. LDN was associated with a statistically significant reduction in PEG in adult chronic pain patients, however the clinical significance is unclear as over 75% of patients discontinued LDN due to lack of benefit.

Vatari Guggulu, Hingvashtaka Churna, and Brihat Saindhavadya Taila in the management of rheumatoid arthritis: An open-label, prospective, single-arm multi-center study

Abstract Background: Despite significant advances in the diagnosis and treatment of rheumatoid arthritis (RA), the clinical outcomes remain unsatisfactory in a significant proportion of patients. Ayurveda management for RA (Amavata) has shown promising clinical outcomes in routine clinical practice and as per published research studies. Objective: The study was designed to assess the therapeutic effect and safety of Ayurveda interventions, Vatari Guggulu (VG), Hingvashtaka Churna (HC), and Brihat Saindhavadya Taila (BS) in the management of RA. Materials and Methods: An open-label, prospective, single-arm multicenter study was conducted at Ayurveda Research Institutes in Patna, Bhubaneswar, and Guwahati with a sample size of 180 participants. Patients of any gender aged 20–60 years with clinically diagnosed RA as per the revised American College of Rheumatology criteria and willing to provide written informed consent to participate in the study were included in the study. Ayurveda interventions, VG, HC, and BS, were administered to the study participants for 12 weeks, with a follow-up at four weeks without intervention. The primary outcome measure was a change in the Disease Activity Score-28 (DAS28) from baseline. The other outcome measures included change in the Indian Health Assessment Questionnaire Disability Index score (HAQ-DI), changes in the acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and change in the quality of life parameters (assessed through the SF-36 questionnaire). Results: A total of 180 participants were enrolled in the study, and data of 179 participants were considered for the final analysis. A statistically significant difference was observed in the outcome parameters, such as a mean change in the DAS28 score, HAQ-DI score, SF-36 score, and ESR and CRP levels (P &lt; 0.001) after 12 weeks of treatment. The mean DAS28 score changed from 6.50 ± 0.790 at baseline to 4.21 ± 1.286 on week 16 follow-up (P &lt; 0.001). No participant withdrew from the study due to adverse events. The trial interventions were well-tolerated and safe. Conclusion: The study outcomes provide preliminary evidence of the safety and potential benefits of the Ayurveda interventions in the management of RA. Further, randomized controlled studies may be planned to generate robust evidence on the therapeutic potential of these interventions so that they can be recommended for use in routine clinical practice. Trial registration: CTRI/2014/12/005242.

Comparison of Echo-Planar Imaging and Compressed Sensing in the Estimation of Flow Metrics from Aortic 4D Flow MR Imaging: A Healthy Volunteer Study.

Prolonged scanning of time-resolved 3D phase-contrast MRI (4D flow MRI) limits its routine use in clinical practice. An echo-planar imaging (EPI)-based sequence and compressed sensing can reduce the scan duration. We aimed to determine the impact of EPI for 4D flow MRI on the scan duration, image quality, and quantitative flow metrics. This was a prospective study of 15 healthy volunteers (all male, mean age 33 ± 5 years). Conventional sensitivity encoding (SENSE), EPI with SENSE (EPI), and compressed SENSE (CS) (reduction factors: 6 and 12, respectively) were scanned.Scan duration, qualitative indexes of image quality, and quantitative flow parameters of net flow volume, maximum flow velocity, wall shear stress (WSS), and energy loss (EL) in the ascending aorta were assessed. Two-dimensional phase-contrast cine MRI (2D-PC) was considered the gold standard of net flow volume and maximum flow velocity. Compared to SENSE, EPI and CS12 shortened scan durations by 71% and 73% (EPI, 4 min 39 sec; CS6, 7 min 29 sec; CS12, 4 min 14 sec; and SENSE, 15 min 51 sec). Visual image quality was significantly better for EPI than for SENSE and CS (P < 0.001). The net flow volumes obtained with SENSE, EPI, and CS12 and those obtained with 2D-PC were correlated well (r = 0.950, 0.871, and 0.850, respectively). However, the maximum velocity obtained with EPI was significantly underestimated (P < 0.010). The average WSS was significantly higher with EPI than with SENSE, CS6, and CS12 (P < 0.001, P = 0.040, and P = 0.012, respectively). The EL was significantly lower with EPI than with CS6 and CS12 (P = 0.002 and P = 0.007, respectively). EPI reduced the scan duration, improved visual image quality, and was associated with more accurate net flow volume than CS. However, the flow velocity, WSS, and EL values obtained with EPI and other sequences may not be directly comparable.

Alteraciones de la motilidad esofágica

Esophageal motility disorders (EMD) manifest clinically with the presence of dysphagia and/or chest pain related to swallowing. In order to diagnose it, it is necessary to first rule out organic causes that would explain these symptoms. In recent decades, the development of high-resolution manometry and its use in routine clinical practice has allowed for better characterization of esophageal motility disorders. The diagnostic criteria have been updated in recent years in the Chicago Classification v4.0, which establishes two large groups of motor disorders: those with esophagogastric junction outflow obstruction (EGJOO) and those with abnormal esophageal body contractility. The treatment of EMDs with EGJOO (the various presentations of achalasia and esophagogastric junction outflow obstruction) is aimed at reducing the baseline pressure in this area. Various techniques are available for this, such as pneumatic balloon dilatation, endoscopic (POEM) and surgical myotomy (Heller myotomy), and, less frequently, the use of oral drugs and botulinum toxin injection. In the case of esophageal peristalsis disorders, the goal of treatment is to control symptoms. To do so, proton pump inhibitors (PPIs) are used in patients with associated gastroesophageal reflux disease (GERD) and, in the case of disorders associated with hypercontractility, other drugs such as nitrates or calcium channel blockers and, occasionally, low-dose tricyclic antidepressants may be used.

Quantification of Measurable Residual Disease Detection by Next-Generation Sequencing–Based Clonality Testing in B-Cell and Plasma Cell Neoplasms

Next generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in post-treatment settings can be crucial for relapse risk stratification in patients with B-cell and plasma cell neoplasms. Prior studies have focused on validation of various technical aspects of the MRD assays, but more studies are warranted to establish the performance characteristics and enable standardization and broad utilization in routine clinical practice. Here, we describe our approach and clinical experience with an NGS-based IGH MRD quantification assay, incorporating a spike-in calibrator for monitoring B-cell and plasma cell neoplasms based on their unique IGH rearrangement status. Comparison of MRD status (positive or undetectable) by NGS and flow cytometry (FC) assays showed high concordance (91%, 471/519 cases) and overall good linear correlation in MRD quantitation, particularly for chronic lymphocytic leukemia and B-lymphoblastic leukemia/lymphoma (R=0.85). Quantitative correlation was lower for plasma cell neoplasms, where underestimation by FC is a known limitation. No significant effects on sequencing efficiency by the spike-in calibrator were observed, with excellent inter- and intra-assay reproducibility within our laboratory, and in comparison to an external laboratory, using the same assay and protocols. Assays performed both at internal and external laboratories showed highly concordant MRD detection (100%) and quantitation (R=0.97). Overall, this NGS-based MRD assay showed highly reproducible results with quantitation that correlated well with FC MRD assessment, particularly for B-cell neoplasms.

Assessing utility of imaging based biomarker to differentiate pathologically classified frontotemporal lobar degeneration syndromes

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) comprises distinct neuropathological entities that present as several overlapping clinical syndromes. Two main pathological inclusions are identified in FTLD – TDP‐43, and tau itself further subdivided into 4 repeat (e.g., PSP‐tau and CBD‐tau) groups. Clinicopathological correlation is poor, at ∼60%. In vivo sensitive and specific biomarkers are needed to improve pathological diagnosis for clinical trials.The midbrain‐pons ratio (MP) is an imaging biomarker that has been shown to differentiate PSP‐tau from Parkinson’s disease and multisystems atrophy, as well as clinically defined progressive supranulclear palsy from other FTLD syndromes.We examined whether the MP at presentation could distinguish PSP‐tau from controls and Alzheimer’s disease (AD), as well as from other FTLD pathologies.MethodParticipants in a clinical cohort‐brain bank program based at Brain and Mind Centre, Sydney, Australia, with FTLD pathologies were included, as were matched healthy Controls and clinically diagnosed AD patients. The midbrain and pons were manually traced from the sagittal MRI slice at the midline at the initial clinical assessment of all the participants for comparison.ResultIn total, 65 participants were included in the study – 42 with FTLD (13 PSP‐tau, 6 CBD‐tau, 23 TDP‐43), 11 AD and 12 control participants; no patients with Pick’s disease were available for inclusion. Only 6/13 PSP‐tau patients, 1/6 CBD‐tau patients and 18/23 individuals with TDP‐43 were clinically diagnosed with PSP, CBS, and FTD respectively. The MP differed significantly in the PSP‐tau group compared to the control, AD, and other FTLD groups, including the CBD‐tau group. Using relevant cut off scores, positive predictive values of 90‐100% were achieved in distinguishing PSP‐tau from controls, AD, and other FTLD pathologies.ConclusionThe MP is a useful in vivo biomarker to identify individuals with PSP‐tau. It can distinguish PSP‐tau from controls, AD, and other FTLD pathologies with high PPVs, even CBD‐tau, another important tauopathy often causing a similar clinical presentation. The PPVs achieved in using the MP were similar to those achieved using CSF and PET biomarkers of amyloid to predict AD pathology. The MP should be considered for routine use in clinical practice and selection into trials of anti‐PSP‐tau therapies.

How Far Should We Investigate the Male Causes in Unexplained Infertility?

According to a recent report by the Guideline Development Group of the ESHRE, the definition of Unexplained Infertility (UI) is ‘infertility in couples with apparently normal ovarian function, fallopian tubes, uterus, cervix and pelvis, age [Formula: see text]40 years and with adequate coital frequency; and apparently normal testicular function, genito-urinary anatomy and a normal ejaculate.’ This is anchored with the ICMART definition of infertility, where couples should have at least 12 months of regular, unprotected sexual intercourse before investigations are initiated. Since Unexplained Infertility is a diagnosis by exclusion, apart from evaluating female causes, it seems important that in evaluating male contributions to the UI, all necessary tests need to be carried out. Unfortunately, there are no robust standardized methods for establishing etiologic diagnosis in the male partner and that in some patients, underlying sperm dysfunction may not be detected during a routine assessment of the ejaculate, which may appear to be normal using the 2021 WHO standards. It is possible that some adverse reproductive outcomes that have been identified during medical and reproductive history examination may require the use of further tests procedures specified in the latest WHO manual to assess sperm function. However, these tests have a research status only or are not regarded for routine use in clinical practice until sound evidence is developed. These tests include testicular imaging, anti-sperm antibodies, sperm DNA fragmentation, sperm chromatin condensation, sperm aneuploidy screening, serum hormone testing, semen HPV testing, and semen microbiology testing all of which were found not routinely indicated based on current evidence when semen was found to be normal using the WHO 2021 semen standards. In summary, in evaluating male causes in unexplained infertility, there are no robust data to support the recommendation that additional tests about the male reproductive function may routinely be carried out when semen analysis based on the 2021 WHO standard is normal. However, additional tests may be carried out when adverse reproductive outcomes and findings in the medical and reproductive history may require the use of these further tests especially when there are no findings on the female side.

Plasma p‐tau forms as potential diagnostic biomarkers for Alzheimer’s disease

AbstractBackgroundAccumulation of tau aggregates is a pathological hallmark of Alzheimer’s disease (AD) that is closely related to the emergence of neurodegeneration and manifestation of clinical symptoms. Currently, CSF and plasma biomarkers of tau pathology, which would improve the diagnostic process in everyday clinical practice and facilitate the classification of patients for clinical trials, are the focus of research. Biomarkers of tau pathology correlate with post‐mortem AD pathology. Furthermore, they allow for differentiation of AD from other types of dementia, and prediction of future progression from normal cognition and mild cognitive impairment to AD. The availability of The clinical utility of novel assays for the detection of several isoforms of tau pathophysiology in the blood, which are currently available, requires verification. Therefore, the aim of the present study was evaluation of tau proteins in the blood of AD patients and non‐demented controls, and assessment of their diagnostic utility.MethodPlasma concentrations of pTau181 and pTau231 were assessed using a Single molecule array (Simoa). CSF biomarkers, including Aβ‐42, Aβ‐42/Aβ‐40, tau and pTau181 were evaluated in 20 AD patients and 18 elderly subjects without cognitive deficits by ELISA technique.ResultStatistically significantly higher blood levels of pTau181 and pTau231 were observed in AD patients in comparison to cognitively normal individuals. Increased concentration of pTau231 correlated with age and MMSE. Furthermore, the associations between the levels of plasma pTau231 and plasma pTau181, CSF Tau and pTau181, as well as Aβ‐42 were observed in the whole study group.ConclusionThe results indicate that plasma P‐tau181 and P‐tau231 may be diagnostic biomarkers that can help to predict cognitive decline and that they hold promise for use in routine clinical practice.

Current use of antiplatelet therapy in the management of acute myocardial infarction: overview of the FRENCHIE national registry

Abstract Background There are many options for antiplatelet therapy (APT) at various stages in the management of acute myocardial infarction (MI) but few contemporary data regarding use in routine clinical practice in unselected patients. Purpose to describe the contemporary use of APT treatments in unselected MI patients. Methods FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is a multicenter observational study (38 centers in France) consecutively enrolling patients with spontaneous MI whose symptoms were &amp;lt; 48 hours. Exclusion criteria were age &amp;lt; 18 years, no health coverage, unstable angina and procedure-related MI. Results Between September 2019 and December 2020, 10190 patients with MI were enrolled. Complete data on APT use were available for 9842 patients. Of these, 54.5% had ST elevation myocardial infarction (STEMI) and 45.5% non-STEMI (NSTEMI). During the first 24 hours, APT use for STEMI and NSTEMI patients, was as follows, respectively: acetylsalicylic acid (ASA) 95.1% and 88.8%, clopidogrel 12.4% and 17.7%, ticagrelor 79.5% and 55.0%, prasugrel 4.8% and 3.6%, GPIIb-IIIa inhibitors 23.8% and 6.5%, Cangrelor 1.1% and 0.8%. Among STEMI patients, 3.2% had undergone thrombolysis, 92.2% primary percutaneous coronary intervention (pPCI) and 4.5% did not have reperfusion during acute phase management. The use of ASA was similar regardless of the initial reperfusion strategy, but that of P2Y12 inhibitors (P2Y12i) was different. Clopidogrel was mainly used in case of thrombolysis, 69.6% of cases, while ticagrelor was mainly used in case of pPCI or medical treatment alone, respectively in 83.9% and 59.7% of cases. GPIIb-IIIa inhibitors were used in 9.3%, 26.2% and 11.4% in patients who had undergone thrombolysis, pCI and medical treatment respectively. At hospital discharge, APT use was as follows, respectively for STEMI and NSTEMI patients: ASA 94.6% and 91.2%, clopidogrel 14.7% and 21.8%, ticagrelor 72.6% and 54.9%, prasugrel 6.9% and 5.7%. The first P2Y12i administered was different from that retained at discharge in 15.4% of STEMI and 12.5% of NSTEMI patients. The most common scenario was switching from ticagrelor to clopidogrel in 64.2% of STEMI patients and 57.2% of NSTEMI patients. No P2Y12i was prescribed at discharge in 3.6% of STEMI patients and 11.3% of NSTEMI patients. Conclusion In contemporary practice in France, P2Y12i use was different according to MI type and to initial reperfusion strategy. GPIIb-IIIa inhibitors were used in more than a quarter of STEMI patients with pPCI. Switching between P2Y12i occurred in 1/8 of patients before discharge and deserves further investigation.

Validation of electrocardiographic artificial intelligence model for outcome prediction in patients with heart failure

Abstract Introduction Although several valuable biomarkers have been introduced for heart failure (HF) patients, their utilization in routine clinical practice is often constrained by cost and limited availability. Electrocardiogram (ECG) is an essential and cost-effective tool for evaluating cardiovascular diseases. We tested artificial intelligence (AI) algorithm analyzing a printed ECG image for the outcome prediction in patients with acute HF. Methods Two tertiary centers prospectively enrolled 1,254 patients with acute HF syndrome. Baseline ECG images were analyzed using a deep learning system called Quantitative ECG (QCG™), which features a CNN-based binary classifier trained to detect several urgent clinical conditions including shock, cardiac arrest, myocardial infarction, and HF, in addition to rhythm diagnosis. Results Patients with reduced left ventricular ejection fraction (LVEF, &amp;lt;40%) had significantly higher QCG scores for LV dysfunction (QCG-LVdys) (0.80 ± 0.20 vs. 0.38 ± 0.27, P &amp;lt; 0.001), and the AUC of QCG-LVdys for low LVEF was 0.884. Fifty-three patients (4.2%) resulted in in-hospital cardiac death (IHCD), and QCG score for critical events (QCG- Critical) was significantly higher in these patients than in survivors (0.57 ± 0.23 vs. 0.29 ± 0.20, P &amp;lt; 0.001). QCG-Critical was an independent predictor for IHCD after adjustment for age, sex, comorbidities, etiology/type of HF, atrial fibrillation, and QRS widening (adjusted OR = 1.68 [95% CI, 1.47 – 1.92], P &amp;lt;0.001, per 0.1). After further adjustments for echocardiographic LVEF and NTproBNP, QCG-Critical was still significantly correlated with IHCD (adjusted OR = 1.59 [95% CI, 1.36 – 1.87], P &amp;lt;0.001, per 0.1). The AUC of QCG-Critical for IHCD was 0.821 which was higher than the AUC of echocardiographic LVEF (P&amp;lt;0.001) or NTproBNP (P=0.07) (Fig 1A). The AUC of the multivariate model with QCG-Critical and other covariates was 0.866 (Fig 1B). During long-term follow-up, patients with higher QCG-Critical scores (&amp;gt;0.5) showed higher all-cause mortality rate compared to those with low QCG-Critical scores (&amp;lt;0.25) (adjusted HR = 2.69 [2.14 – 3.38], P &amp;lt; 0.001) (Fig 2). Conclusion Predicting outcomes in patients with acute HF appeared feasible using the newly developed Quantitative ECG (QCG) scores. These results suggest the possibility that QCG may serve as a novel biomarker for HF patients.ROC curves for In-hospital cardiac deathSurvival curves according to QCG scores

Cost-minimisation analysis of chronic lymphocytic leukemia in Spain in the era of oral targeted therapies

ObjectiveChronic lymphocytic leukaemia places a considerable economic burden on the Spanish National Health System. This study estimated the direct costs of chronic lymphocytic leukaemia oral targeted therapies from 2011 to 2025, inclusive, in a scenario with fixed treatment oral targeted therapies and in a scenario without them. MethodThe clinical course of adult chronic lymphocytic leukaemia patients was represented by a Markov model with four health states: watchful waiting, first-line treatment, relapse, and death. The treatment pattern was defined according to patient type by disease status or situation, age, presence or absence of deletion in the short arm of chromosome 17, immunoglobulin heavy chain mutation status, and year of treatment. The treatment algorithm was simulated from 2011 to 2025, and included therapies funded by the Spanish National Health System and their use in routine clinical practice, validated by leading experts. A single treatment option was assumed for each type of patient and time period (the most widely option used at each time point). Direct costs were included: pharmacological, administration, tests performed, routine visits, hospitalizations, and adverse events. ResultsFrom 2011 to 2025, there would be a mean annual chronic lymphocytic leukaemia prevalence of 16,436 patients in the scenario without fixed treatment oral targeted therapies and 16,413 in the scenario with fixed treatment oral targeted therapies. In the same period, the total costs in the scenario without fixed treatment oral targeted therapies would be €4,676.7 million and in the scenario with fixed treatment oral targeted therapies they would be €4,111.8 million. Thus, the introduction of fixed treatment oral targeted therapies would entail a saving of €564.9 million (12.1% of the total cost of care of chronic lymphocytic leukaemia patients during the period assessed). In this period, the total cost per patient would decrease from €266,019 in the scenario without fixed treatment oral targeted therapies to €236,852 in the scenario with fixed treatment oral targeted therapies, representing a saving of €29,167 per patient. ConclusionsThis study estimates that, between 2011 and 2025, the introduction of fixed treatment oral targeted therapies for the treatment of chronic lymphocytic leukaemia would entail €564.9 million cost savings for the Spanish National Health System (12.1% of the total cost of care of chronic lymphocytic leukaemia patients during the period assessed).

Development and initial validation of the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses.

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users' mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user's mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies.

Type I and type IIb autoimmune chronic spontaneous urticaria: Using common clinical tools for endotyping patients with CSU.

Mechanisms triggering the pathogenesis of chronic spontaneous urticaria (CSU) have been identified as type I autoallergic (which is associated with IgE antibodies against autoantigens) and type IIb autoimmune (which is driven by autoantibodies to FceR1 and/or IgE). Our aim was to define presumptive endotypes in patients with CSU by using tests amenable to use in routine clinical practice. A retrospective analysis of the medical records of 394 patients with CSU with or without chronic inducible urticaria or angioedema was performed. Patients were assigned to 1 of 4 groups as follows: (1) type I endotype of CSU, if they presented at least 1 of the following: allergic disease, total IgE level of at least 40UI/mL, and positive result of skin tests to inhalant allergen(s), (2) type IIb endotype of CSU, if they presented at least 1 of following: autoimmune disease, low total IgE level less than 40 IU/mL, positive autologous serum skin test result, positive for antinuclear antibodies in a titer of at least 1:160, and elevated level of anti-thyroid peroxidase, (3) overlap of type I/type IIb endotypes of CSU, if they presented with at least 1 marker of both type I and type IIb, and (4) non-type I/type IIb endotype of CSU, if they presented with none of the markers of type I or type IIb. The mean age at onset of symptoms was 34 years; 82.2% of those with CSU were female, and angioedema and chronic inducible urticaria were found in 74.8% and 31.9% of patients, respectively. Of the patients with CSU, 38% presented with the type I endotype and 51% presented with type I/type IIb overlap, whereas 9% presented with the type IIb endotype and 2% presented with the non-type I/type IIb endotype. Eosinopenia was associated with type IIb and type I/type IIb overlap as opposed to the type I and non-type I/type IIb endotypes (P= .02). Most patients with CSU presented with features of the type 1 (autoallergic) endotype, whether associated with type IIb (autoimmune) endotype or not.

The role of cellular immunity and systemic inflammation indices in the pathogenetic mechanisms of mental disorders

To date, inflammatory mechanisms are known to be involved in neuronal damage and increased risk of associated mental disorders, but most previous work has focused primarily on cytokines and other inflammatory markers that are difficult to replicate and not economically feasible for use in routine clinical practice. Other extremely important indicators of the systemic inflammatory process are circulating blood cells and changes in their number, composition, and ratio. Hematologic indices of systemic inflammation (HISI) are already used in somatic specialties: neutrophil-lymphocyte (NLR), monocyte-lymphocyte (MLR) and platelet-lymphocyte (PLR) ratios, as well as the Systemic Immune Inflammation Index (SII) and the System Inflammation Response Index (SIRI). In the context of psychopathology, the HISI require additional investigation, which makes it necessary to pay more attention to the possible mechanisms underlying their changes. The article provides data on the contribution of each cellular element to the mechanism of neuroinflammation and neurodegeneration and on their role in the development of psychopathological processes.

Safety and Efficacy of Ixekizumab in Chinese Adults with Moderate-to-Severe Plaque Psoriasis: A Prospective, Multicenter, Observational Study.

Psoriasis, an incurable chronic inflammatory disease, affects over 6 million people in China. Ixekizumab, a monoclonal antibody against interleukin-17A, has demonstrated efficacy and safety for the treatment of moderate-to-severe plaque psoriasis, although limited data are available regarding its use in routine clinical practice in China. We investigated the real-world application of ixekizumab in China. Adults (≥18 years) with moderate-to-severe plaque psoriasis prescribed ixekizumab in routine clinical practice were enrolled in this prospective, observational, single-arm, multicenter, post-marketing surveillance study. The primary endpoint was the safety of ixekizumab at week 12. The effectiveness of ixekizumab, based on the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), was assessed as a secondary endpoint. In total, 666 patients were enrolled; 663 were included in the safety analysis, and 612 in the effectiveness analysis. At least one adverse event (AE) was reported by 42.7% (283/663) of patients, most of which were mild (242/283, 85.5%), and 32.7% (217/663) of patients reported AEs related to study treatment. The most frequently reported AEs were injection site reactions. AEs led to discontinuation in five patients (0.8%). Only three patients had a serious AE. Mean±standard deviation (SD) change from baseline in PASI score was reduction in 10.79±9.55 at week 2 and 16.80±12.15 at week 12. At week 2, 63.7% of patients achieved PASI 50. At week 12, 93.2%, 77.4%, and 45.1% of patients achieved PASI 75, PASI 90, and PASI 100, respectively. Mean±SD change from baseline in DLQI was reduction in 5.91±6.27 at week 2 and 9.76±7.16 at week 12. DLQI 0/1 was achieved by 19.8% and 59.9% of patients at week 2 and 12, respectively. Ixekizumab was well tolerated and effective in real-world clinical practice in Chinese adults with moderate-to-severe plaque psoriasis.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients

ObjectivesThe skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. MethodsA total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. ResultsIn a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726–0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739–0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. ConclusionsThe incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.